Fundamental details of the system for outflow of aqueous humor remain unknown, yet more knowledge seems vital to full comprehension of the pathogenesis of various types of glaucoma, and to potential improvements in treatment of glaucoma, or possibly its prevention. To learn more about these potentially vital details, we propose to examine intensively certain of the properties of the endothelial cells of the corneoscleral trabecular meshwork, which are most intimately involved in aqueous outflow and which may well be highly influential in control of intraocular pressure. We propose in cats and monkeys to investigate the proliferative and synthetic capabilities of these cells, following quantitatively by autoradiography and electron microscopy their mitosis and the synthesis and deposition of glycosaminoglycans, collagen and glycoproteins by these cells. We propose to perform related histochemical studies on animal eyes and also on excised human eyes, both normal and glaucomatous, to determine the location and concentration of specific varieties of the glycosaminoglycans. In animals we will investigate the immediate and long-term fate of trabecular endothelial cells after injection of inert particles into the anterior chamber, and after exposure to degradative enzymes and surgical injury. Later, we will establish trabecular cells in tissue culture, where their synthetic activity and responses to iris pigment particles, drugs and poisons will be studied. The establishment of a readily available animal system in which to study the various aspects of angle development and cell biology, (especially regarding how these cells respond to pigment and exfoliation material) might well be the most important single step in attempts to understand the mechanism of various open-angle glaucomas. Our studies in the cat suggest that this animal may provide such a system.